The primary purpose of the Organic Synthesis Facility (OSF) is to produce the highest quality synthetic molecules for Fox Chase Cancer Center (FCCC) investigators with peer-reviewed funding. Small organic molecules are used in many areas of research as specific reagents including those that are inhibitors of enzyme activity or protein binding. Some of these molecules have been used in the development of prodrugs against target proteins identified at FCCC. Analogs of natural substrates have been used to probe enzyme mechanism, to investigate protein function, or to test specific hypotheses. The molecules synthesized by the Facility are not purchasable from chemical companies, and custom synthesis from commercial enterprises is either not available or prohibitively expensive. Many of the molecules requested by investigators are novel and require the design of new synthetic routes and purification schemes. For molecules that have been previously synthesized, the Facility uses the published synthetic protocol. However, in more than 50% of these cases, the literature protocol either does not work as described or does not yield a sufficiently pure product and the Facility has to design new syntheses or purification schemes. During the last grant period (2000-2004), 32 different chemical syntheses were completed including eight novel compounds. The compounds synthesized were very diverse in structure and included a tamoxifen metabolite, a gadolinium complex, an antimycin analog, tritium-labeled estramustine, bromo naphthalenesulfonic acid and spin-labeled hydrazone. The synthesis of several novel inhibitors of retroviral integrases (AIDS Res. Hum. Retro. 20:135-144, 2004) exemplifies the quality science generated by the OSF. Seventeen articles, three co-authored by OSF staff, published in peer-reviewed journals from 2000-2004 used compounds that were synthesized in the OSF. The number of investigators with peer-reviewed funding using the OSF has increased from 25 in 2000 to 34 in 2003 (36%). Usage in 2003 was from all 11 Programs and 98% of use was by investigators with peer-reviewed funding. This usage includes syntheses, purification of reagents, chemical analysis, and consultation. Fifty-one (51) investigators with peer-reviewed funding utilized products and services from the OSF during the Core Grant period (2000-2004).